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A limited study provides a glimpse of clarity on HDL functionality

11-01-2018, 04:58 AM

I thought that the below study provided some clarity on HDL functionality. In much the same way that apoCIII hinders clearance of some vLDL particles (which then likely become sdLDL), it also hinders clearance of HDL particles. The ideal case is for the LDL family and HDL particles to do their job and then get expeditiously cleared by the liver. In that case HDL-C levels could represent an accurate picture of potential risk going forward in time. There is probably some evolutionary reason why apoCIII is biologically necessary, but excess levels increase the risk for CVD. When a person has higher triglycerides (> 130 mg/dL), they seem to produce more apoCIII. There is an anti-sense drug to reduce apoCIII levels under development, but that will take several more years even if all goes well in Phase II and Phase III trials. There currently isn't a publicly available assay to test apoCIII levels, but I think that one must be coming as there wouldn't be an easy way to tell who would need to get the apoCIII lowering drug. In the meantime, I personally plan to keep my triglyceride levels well below 100 mg/dL.

Comment

Here is another recent study which indicates why we need to pay more attention to triglyceride levels and less attention to LDL-C and HDL-C as absolute markers for future risk. Below is an excerpt from the Intro section (note: apoA-1 is for an HDL particle and apoB is for an LDL particle):

"Lipoproteins are micelle-like particles transporting neutral lipids in blood and extracellular fluid. Metabolic functions of lipoproteins are mostly controlled by interactions of apolipoproteins (apo) presented on the particles’ surfaces with cell membrane receptors, enzymes, and lipid transfer proteins. Their central role in lipid metabolism links apos to diagnosis and treatment of dyslipidemias and atherosclerotic cardiovascular disease (ASCVD). In this regard, apoA-I and apoB were proposed as markers superior to HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) for the assessment of cardiovascular risk, advocating the relevance of quantifying apos in the clinical routine [1,2]. Besides, apoC-III, a potent modulator of lipoprotein lipase (LPL), was identified as risk marker of incident coronary artery disease (CAD) [3], which is in line with current evidence on a causal role of triglyceride-rich lipoproteins (TRL) and TRL remnants in ASCVD [4, 5, 6]. ApoE isoforms [7], especially apoE2 and apoE4, as well as apoA-IV, which was found to be inversely correlated with CAD [8, 9, 10], are further biomarkers of ASCVD."